Abstract
Introduction
Degenerative disk disease (DDD) is a medical condition whereby the intervertebral discs (IVD) of the human spine degenerates and causes pain which significantly affects the quality of one's life. A highly possible approach to overcome this problem is to produce injectable microspheres of similar composition to the native NP using MSCs to restore both its structural and functional properties. However, there is no systematic study in identifying the optimal conditions and signals for inducing MSCs differentiation toward nucleus pulposus (NP)-like phenotype.
Materials and Methods
In this project, we attempt to study the possibility to construct injectable microspheres with properties highly similar to that of native NP tissue using MSCs. Our approach was to culture NPCs within collagen microspheres whilst maintaining their phenotype and other characteristics, so that they would remodel the matrix microenvironment to one that was conducive for MSCs differentiation into new NPCs when MSCs were introduced upon removal of the original NPCs. Particular attention will be paid to the interaction between the MSCs and NPC-produced ECM to understand the mechanism for MSC differentiation.
Results
We demonstrated that NPCs could maintain survival within the collagen microspheres and produce NP-like ECM such as glycosaminoglycan (GAG) and Type II Collagen. GAG productions of NPCs were also found to positively correlate to the dosage of TGF-βwithin a period of 6 days. An optimized decellularization protocol was established to completely remove the encapsulated NPCs with partial retention of the GAG-rich matrix. The decellularized microspheres were able to be repopulated with hMSCs. With the effects of acellular matrices, these hMSCs were able to produce new NP-like ECM according to the results of histological, biochemical, immunohistological analysis, and real-time PCR.
Conclusion
The NPC derived acellular matrix is able to support growth of hMSC. Ongoing efforts are to assess the potential of the NPC-constituted matrices to induce MSC differentiation into the NPC lineage.
Yes
None declared